The general purpose of the proposed research is to study the genetic nature of enterotoxin production in epidemic strains of Escherichia coli and other enteric organisms. The major premise of the research is that capacity of enteric organisms to synthesize enterotoxins and other substances which add materially to bacterial pathogenicity are often associated with extrachromosomal genetic elements called plasmids. A number of plasmids including Ent, K88, and K99 have been isolated which determine the biosynthesis of enterotoxin, and K antigens which permit an infecting organism to colonize a specific animal host. Support is requested to extend these findings and to define more precisely the genetic and molecular nature of these plasmids and their contribution to bacterial pathogenicity. Additionally, methods are described which have permitted the isolation of the structural genes for enterotoxin biosynthesis and K antigen biosynthesis on small composite plasmids so that the nature and the control of these substances may be examined in vitro. Most cases of acute gastroenteritis are not associated with any well-recognized bacterial or viral pathogen. Several lines of evidence have incriminated members of the "normal" intestinal flora as the culprits. The research proposed here attempts to define the genetic basis for the capacity of these microorganisms to cause disease and to define ways for the development of preventive measures to control these infectious agents.